title: Autocrine role of interleukin-13 on skeletal muscle glucose metabolism in type 2 diabetic patients involves microRNA let-7.
abstract: Low-grade inflammation associated with type 2 diabetes (T2DM) is postulated to exacerbate insulin resistance. We report that serum levels, as well as IL-13 secreted from cultured skeletal muscle, are reduced in T2DM vs. normal glucose-tolerant (NGT) subjects. IL-13 exposure increases skeletal muscle glucose uptake, oxidation, and glycogen synthesis via an Akt-dependent mechanism. Expression of microRNA let-7a and let-7d, which are direct translational repressors of the IL-13 gene, was increased in skeletal muscle from T2DM patients. Overexpression of let-7a and let-7d in cultured myotubes reduced IL-13 secretion. Furthermore, basal glycogen synthesis was reduced in cultured myotubes exposed to an IL-13-neutralizing antibody. Thus, IL-13 is synthesized and released by skeletal muscle through a mechanism involving let-7, and this effect is attenuated in skeletal muscle from insulin-resistant T2DM patients. In conclusion, IL-13 plays an autocrine role in skeletal muscle to increase glucose uptake and metabolism, suggesting a role in glucose homeostasis in metabolic disease.
authors.affiliation: Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Lake Q
authors.initials: LQ
authors.lastname: Jiang
authors.forename: Niclas
authors.initials: N
authors.lastname: Franck
authors.forename: Brendan
authors.initials: B
authors.lastname: Egan
authors.forename: Rasmus J O
authors.initials: RJ
authors.lastname: Sjögren
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Katayama
authors.forename: Daniella
authors.initials: D
authors.lastname: Duque-Guimaraes
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Anna
authors.initials: A
authors.lastname: Krook
mesh_terms: D019898:Autocrine Communication / Q000187:drug effects / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture
chemical_list: D017077:Culture Media, Conditioned; D018793:Interleukin-13; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D005947:Glucose
keywords: cytokines; diabetes; gene expression; glucose metabolism; lipid metabolism